NSAIDs attenuate hyperalgesia induced by TRP channel activation.

Ivliane Nozadze,Merab G Tsagareli,Gulnaz Gurtskaia,Nana Tsiklauri

doi:10.1016/j.dib.2015.12.055

Abstract

Transient receptor potential (TRP) cation channels have been extensively investigated as targets for analgesic drug discovery. Because some non-steroidal anti-inflammatory drugs (NSAIDs) are structural analogs of prostaglandins (mediators of inflammation) and NSAIDs attenuate heat nociception and mechanical allodynia in models of inflammatory and neuropathic pain, we examined three widely used NSAIDs (diclofenac, ketorolac, and xefocam) on the activation of TRPA1 and TRPV1 channels using thermal paw withdrawal (Hargreaves) test and mechanical paw withdrawal (von Frey) test in male rats. Thermal withdrawal latencies and mechanical thresholds for both hind paws were obtained with 5, 15, 30, 45, 60, and 120 min intraplantar post-injection of TRPA1 agonizts, allyl isothiocyanate (AITC) (a natural compound of mustard oil) and cinnamaldehyde (CA), and TRPV1 agonist capsaicin or vehicle. Twenty minutes prior to the start of the experiment with TRP agonizts, diclofenac, ketorolac or xefocam were pre-injected in the same hindpaw and animals were examined by these two tests. After pretreatment of all three NSAIDs in the ipsilateral (injected) hindpaw that produced strong antinociceptive effects, AITC, CA, and capsaicin caused significant decreases in latency of the thermal withdrawal reflex compared with vehicle or the contralateral hindpaw. The same findings were observed for the paw withdrawal threshold. In approximately 30 min the effects of CA, AITC, and capsaicin returned to baseline. The data are different from our previous evidence, where TRPA1 agonizts AITC and CA and TRPV1 agonist capsaicin produced hyperalgesia for nearly 2 h and resulted in facilitation of these withdrawal reflexes (Tsagareli et al., 2010, 2013). Thus, our data showing that NSAIDs suppress thermal and mechanical hyperalgesia following TRP activation could presumably due to inactivation or desensitization of TRPA1 and TRPV1 channels by NSAIDs.

Highlights

Because some non-steroidal anti-inflammatory drugs (NSAIDs) are structural analogs of prostaglandins and NSAIDs attenuate heat nociception and mechanical allodynia in models of inflammatory and neuropathic pain, we examined three widely used NSAIDs on the activation of TRPA1 and TRPV1 channels using thermal paw withdrawal (Hargreaves) test and mechanical paw withdrawal test in male rats
Our data showing that NSAIDs suppress thermal and mechanical hyperalgesia following transient receptor potential (TRP) activation could presumably due to inactivation or desensitization of TRPA1 and TRPV1 channels by NSAIDs
We found that ketorolac pretreatment inactivates TRPA1 channels to its agonizts, allyl isothiocyanate (AITC) and CA, and results in the return of hyperalgesia to baseline in approximately 30 minutes

Summary

Data accessibility

Raw Latency of thermal paw withdrawal latency and mechanical paw withdrawal threshold. We examined three widely used non-steroidal anti-inflammatory drugs (NSAIDs) (diclofenac, ketorolac, and xefocam) on the activation of transient receptor potential (TRP) channels (TRPA1 and TRPV1) to its agonizts, allyl isothiocyanate (AITC, main compound of mustard oil), cinnamaldehyde (CA), and capsaicin in behavioral experiments in rats. Recent data in the field of pain research have established a subset of thermo-TRP channels that are capable of initiating sensory nerve impulses following the detection of thermal, as well as mechanical and chemical irritant stimuli These irritants include menthol, capsaicin, cinnamaldehyde (CA), mustard oil, and others [3,4,6,8,10]. Equivalent findings were observed for the paw withdrawal threshold to mechanical stimulation (Fig. 2C) In both tests, the effects of capsaicin returned to baseline in approximately 45 min. We suggest that presented data indicate a novel mechanism involving the anti-inflammatory and analgesic effects of NSAIDs, which may be involved in direct inactivation or desensitization of TRPA1 and TRPV1 channels and could be used for development novel class of analgesics

Animals

Application of chemicals

Behavioral testing

Findings

Data analysis